HEMATOPOIESIS AND ERYTHROPOIESIS Chapters 3 and 4

Red bone marrow is composed of

"cord" of tissue where the blood cells are produced

Produced by many different cells Stimulate specific cell growth

Colony stimulating factors (CSFs)

Supravital stain

A stain used to stain cells while they are still living

if stained with Wright stain it's called Wright stain is the standard stain used in hematology

polychromasia

Erythropoiesis

process of erythrocyte production

Hematopoiesis

production and development of blood cells

Maturing Cells

takes about 7-10 days live for about 120 days in the peripheral blood stream

Normoblastic Rubriblastic Erythroblastic

3 Nomenclatures for Erythropoiesis

Nucleus: Round to oval Nucleoli no longer visible Chromatin more clumped Cytoplasm: Deeply basophilic No Granules

Basophilic Normoblast (prorubricyte)

In adults (almost all) blood cell development occurs in

Bone Marrow

The determining factor controlling the rate of production is physiologic need Stem cell regulators stem cells divide when stimulated by certain

Cytokines

Cytokines

Cytokines are diverse group of glycoproteins that regulate functional activities of cells Sometimes called "growth factors" Responsible for stimulation or inhibition of production, differentiation, or trafficking of blood cells Produced by many types of cells (incl. WBC) Can prevent apoptosis

Quiescence of HSC and early progenitors

TGF-β

Suppresses colony growth

TNF-α

Nurse cells surrounded by concnentric circles of maturing erythrocytes. Aids in the ejection of the nucleus Phagocytizes defective cells

Erythroblastic Islands

Stimulates proliferation and differentiation of erythrocytes Stimulates BFU-E to develop into CFU-E Produced primarily by specialized cells in the kidney Responds to hypoxia (lack of oxygen) to maintain adequate levels of erythrocytes to carry hemoglobin (oxygen)

Erythropoietin

Structural support (collagen) Adhesion (integrins and VCAM)

Extracellular Matrix

Erythropoiesis

Formation and maturation of erythrocytes

These cell give rise to all bone marrow cells (erythrocytes, leukocytes, platelets) Capable of self-renewal and differentiation into progenitor cells (asymmetric cell division) Not morphologically distinguishable

Hematopoietic STEM cell

Starts at about week 5 The liver becomes the primary site of hematopoiesis by third month. Spleen is a minor site during this phase Continues to produce cells until birth

Hepatic phase

Induce cell death

Interferons

Varying source and target sites Promote differentiation of WBCs

Interleukins

Activation is essential in early stages of hematopoiesis Stimulates stem cell and progenitor production

Kit ligand (aka stem cell factor)

Main function is not related to hematopoiesis but plays a role in the destruction of erythrocytes Backs up the spleen

Liver

Lymphoid tissue - lymphocytes activation and proliferation

Lymph Nodes

Nucleus: None Cytoplasm: Salmon pink color Pale area in the center called the central pallor

Mature Erythrocyte

95% of bone marrow cells Are morphologically distinguishable

Maturing cells

From birth until 5-7 years old hematopoiesis occurs in the red bone marrow of ALL bones After this point fat or yellow marrow begins to replace the red marrow of long and short bone By the time we are adult the only site of hematopoiesis is flat and irregular bones

Medullary Phase

Before birth, embryonic Starts as early as day 19 of fertilization Hematopoiesis is occurring in the yolk sac of the embryo And in tissues near the embryonic aorta (aorta-gonad-mesenphros)

Mesoblastic phase

Colonies of differentiated cells remain fairly segregated

Niches

N:C ratio

Nuclear to cytoplasm ratio, the ration of the volume of the cell nucleus to the volume of the cells cytoplasm

Nucleus: May be central or eccentric Chromatin tightly condensed Cytoplasm: Reddish pink

Orthochromic Normoblast (metarubricyte)

Nucleus: No nucleus Cytoplasm: Residual mitochochondria and RNA Overall blue appearance

Reticulocyte

Nucleus: Smaller Chromatin is clumped and dense Cytoplasm: Some pink coloration giving the cell a blue-gray or light gray appearance Last stage capable of mitosis

Polychromatic Normoblast (rubricyte)

Have potential to be any hematopoietic cell 3% of bone marrow cells Not morphologically distinguishable

Progenitor cells

Nucleus: Round to oval 1 to 2 nucleoli Fine chromatin Cytoplasm: Deeply basophilic No granules

Pronormoblast (Rubriblast)

Largest lymphoid organ in the body Plays the role of "dumping site" for old and defected erythrocytes Storage site for thrombocytes (platelets) Vital but not essential for life

Spleen

Macrophages in the bone marrow

Stem cell inhibitor (SCI)

Homing receptors Secrete growth and differentiation factors

Stromal Cells

Inclusions

Structures formed within a cell not normally found

Cellular regulation

T cells and NK cells

Mesoblastic Hepatic Medullary or myeloid

Three phases of hematopoiesis

Controls production and release of platelets Liver is main site of production

Thrombopoietin (TPO)

Lymphoid tissue - produces T-lymphocytes

Thymus

Blood cells move...

between reticular cells and through endothelial cells in the sinus wall

Erythrocyte

red blood cell

contains mainly red blood cells and macrophages function to phagocytize old red blood cells

red pulp

if stained with supravital stain (stains living cells) it's called

reticulocyte

circular in structure and is made up mainly of lymphocytes functions in a manner similar to the nodules of the lymph node

white pulp